PROJECT SUMMARY/ABSTRACT By the time they finish high school, approximately half of all high school-aged adolescents have tried illicit substances at least once in their lifetime. During adolescence, the brain undergoes rapid development and maturation, which may be disrupted by alcohol and substance use. The majority of investigations in this area have focused on the effects of heavy use by recruiting individuals who are in treatment for an alcohol or substance use disorder. Therefore, there is relatively little information on the effects of more normative use of alcohol and substances during adolescence. Further, there has been very little work done to investigate the relationship between race and sex differences and the effects of alcohol and substance on the brain. The long- term goal of the current project is to better understand the impact of alcohol and substance use on the developing brain and to use that knowledge to improve targeted prevention and intervention efforts. The proposed project will investigate the central hypothesis that alcohol and substance use during adolescence has diffuse effects on brain structure and function which can be seen in emerging adulthood, particularly within regions of the prefrontal cortex (PFC) and hippocampus. The central hypothesis will be addressed by examining: 1) the relationship between adolescent alcohol and substance use and functional brain connectivity in young adulthood; 2) the relationship adolescent alcohol and substance use has to brain structure in young adulthood; and 3) the impact race and sex differences in the neural outcomes of alcohol and substance use. Accomplishing these three aims will provide a more comprehensive understanding of adolescent alcohol and substance use and its effects on the brain, as well as provide insight into whether race or sex differences exist in the neural effects of such use. The aims of the proposed project will be completed in conjunction with a formal research training plan, sponsored by Dr. David Knight, Dr. Sylvie Mrug, and Dr. Karen Cropsey. The training plan focuses on developing 1) expertise in alcohol and substance use research; 2) knowledge and skills in MRI methods and techniques; 3) statistical skills to interpret longitudinal data; 4) scientific writing and presentation; and 5) mentorship skills and experience. Completing the current project will provide a solid foundation for the applicant's career as an independent investigator.